Journal
NANOTOXICOLOGY
Volume 5, Issue 4, Pages 479-492Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/17435390.2010.540356
Keywords
Blood-brain-barrier; neuroinflammation; gold nanoparticles; brain microvessel endothelial cells; neurotoxicity
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Funding
- U. S. Air Force Research Laboratory at the National Center for Toxicological Research/FDA
- U. S. Department of Energy, U. S. Air Force Research Laboratory/RHPB
- U. S. Food and Drug Administration/NCTR
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This report examined blood-brain barrier (BBB) related proinflammatory mediators and permeability changes in response to various sized gold nanoparticles (Au-NPs) (3, 5, 7, 10, 30 and 60 nm) in vitro using primary rat brain microvessel endothelial cells (rBMEC). The Au-NPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and laser Doppler velocimetry (LDV). The accumulation of Au-NPs was determined spectrophotometrically. The rBMEC cytotoxicity of Au-NPs was evaluated by cell proliferation assay (XTT) (concentration range 0.24-15.63 mu g/cm(2), for 24 h). The time-dependent changes (0, 2, 4 and 8 h) of several proinflammatory mediators (IL-1 beta, IL-2, TNF alpha and PGE(2)) were evaluated by ELISA. The smaller Au-NPs (3-7 nm) showed higher rBMEC accumulation compared to larger Au-NPs (10-60 nm), while only moderate decreased cell viability was observed with small Au-NPs (3 nm) at high concentrations (>= 7.8 mu g/cm(2)). Even though slight changes in cell viability were observed with small Au-NPs, the basal levels of the various proinflammatory mediators remained unchanged with all treatments except LPS (positive control). rBMEC morphology appeared unaffected 24 h after exposure to Au-NPs with only mild changes in fluorescein permeability indicating BBB integrity was unaltered. Together, these data suggest the responses of the cerebral microvasculature to Au-NPs have a significant relationship with the Au-NPs unique size-dependent physiochemical properties.
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